English Version
M. Vargas · G. Servillo

Paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria

Schlüsselwörter Paroxysmal nocturnal haemoglobinuria (PNH); ICD 10: D59.6; Marchiafava-Micheli disease
Keywords Paroxysmal nocturnal haemoglobinuria (PNH); ICD 10: D59.6; Marchiafava-Micheli disease
Zusammenfassung Dieser Beitrag enthält keine Zusammenfassung

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal haematopoietic stem cell disease caused by somatic mutations in the PIGA gene (Xp22.1), encoding a protein involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor.

The mutation occurs in one or several haematopoietic cells and leads to a lack (total or partial) of all GPI-anchored cell membrane proteins (the most important being CD55 and CD59). PNH had a prevalence of up to 1.6/100,000, a 5-years mortality about 35 % and a median survival of 10–5 years. After bone marrow transplant, the majority of deaths occur within the first years of transplantations while the probability to survive at 2 years is 56 %. Symptoms and complications of PNH are caused by the deficiency of CD55 and CD59, proteins regulating and stabilising the complements cascade, on PNH erythrocytes. The lack of CD55 and CD59 is responsible for a complement mediated intravascular haemolysis mainly associated to haemoglobinuria, thrombosis and bone marrow failure. Furthermore, cell-free plasma haemoglobin in PNH leads to depletion of nitric oxide causing smooth muscle dystonia and altering the vascular tone. For these reasons, in a clinical context, haemolysis of PNH is associated with anaemia, weakness, dyspnoea, fatigue, renal impairment, need for transfusions, pulmonary hypertension, abdominal pain and thromboembolic complications. The main anaesthetic concerns in PNH consist in preventing the activation of complement cascade during the peri-operative period. Any stressful situations may activate or exacerbate the complement cascade. An optimal peri-operative management of patients with PNH includes the use of eculizumab, a novel antibody blocking the terminal complement cascade, blood cells transfusion and antibiotic prophylaxis, the avoidance of hypoxaemia, acidosis, dehydration and drugs known to activate complement cascade.